Abstract
Alcohol dehydrogenases of yeast and mouse liver differ in their relative sensitivity to inhibition by pyrazole and 4-brompyrazole. Yeast alcohol dehydrogenase is relatively insensitive to 4-brompyrazole. The K1 for pyrazole is 1.1 x 10-5 M; for 4-brompyrazole, 1.1 x 10-3 M. Both inhibit competitively with ethanol. Yeast alcohol dehydrogenase can be used for assay of blood alcohol in pyrazole-treated mice. Mouse liver alcohol dehydrogenase is strongly inhibited by both compounds. The K1 for pyrazole is 8 x 10-7 M, competitive with ethanol, and for 4-brompyrazole, 3 x 10-7 M, competitive or mixed type inhibition. Pyrazole has a half-life of about 10 hours and 4-brompyrazole about three hours in mice, as estimated from alcohol elimination rates. The LD50 after single i.p. injections of pyrazole in mice is 7.9 mmol/kg; for 4-brompyrazole, 2.5 mmol/kg. Thus the ratio of efficacy to toxicity is about the same for the two compounds, but 4-brompyrazole has a shorter duration of action.
Footnotes
- Received February 1, 1971.
- Accepted March 29, 1971.
- © 1971, by The Williams & Wilkins Company
JPET articles become freely available 12 months after publication, and remain freely available for 5 years.Non-open access articles that fall outside this five year window are available only to institutional subscribers and current ASPET members, or through the article purchase feature at the bottom of the page.
|